Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases, and cancer, today announced updates on its lead product candidates, XmAb®5871 and XmAb®7195, and on its XmAb® bispecific oncology pipeline. Updates are being presented today at its R&D Day for analysts and investors in New York, NY.
"We are happy to report on the progress and expansion of our proprietary pipeline of XmAb antibodies," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "Today we will discuss the planned open-label pilot study of XmAb5871 in the rare autoimmune disorder IgG4-related disease (IgG4-RD), and provide an update on our progress for XmAb7195. We have added additional cohorts to the ongoing Phase 1a study of XmAb7195 and started this next phase of the trial, in which subjects will receive two infusions of XmAb7195, allowing us to examine IgE reduction and the safety profile in this setting. Further, we plan to initiate a Phase 1 study with a subcutaneous formulation of XmAb7195 in 2016. We have also selected our second bispecific antibody, XmAb13676, which will enter clinical testing for B-cell malignancies in 2016. This CD20xCD3 bispecific molecule is the beginning of a planned expansion of our bispecific oncology pipeline."
XmAb5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain and that uses Xencor's proprietary XmAb immune inhibitory Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. The Company reported Phase 1b/2a data in rheumatoid arthritis (RA) patients at the European League Against Rheumatism (EULAR) 2015 Annual Meeting on June 10, 2015, which showed promising trends in improvement in RA disease activity by multiple disease activity measures and across multiple dose groups. The Company believes that XmAb5871 has potential clinical application across a number of autoimmune diseases, including IgG4-Related Disease (IgG4-RD), for which Xencor expects to initiate an open-label pilot study later in 2015.
Today, Xencor will provide an overview of its development plans for XmAb5871 for the treatment of the rare autoimmune disorder IgG4-RD. This open-label pilot trial will enroll approximately 15 subjects, treatment will continue for up to 24 weeks and the recently reported IgG4-RD Responder Index will be used to assess treatment activity (Carruthers 2012, International Journal of Rheumatology). Xencor's planned lead investigator, John Stone, M.D., Ph.D., Professor of Medicine at Massachusetts General Hospital, will present background and insights from his experience in treating IgG4-RD patients.
XmAb7195 is a monoclonal antibody in Phase 1a development as a potential treatment for allergic asthma. XmAb7195 targets IgE with its variable domain and uses Xencor's XmAb immune inhibitor Fc domain to target FcγRIIb, resulting in three distinct mechanisms of action for reducing IgE levels. In multiple animal models, XmAb7195 has been shown to rapidly reduce free and total IgE and block production of IgE by immune cells.
Today, Xencor announced commencement of an expansion of the Phase 1a trial of XmAb7195, in which subjects will receive two doses of XmAb7195. This new part of the trial will allow the Company to examine IgE reduction and the safety profile of XmAb7195 after a second infusion. Data from this trial is expected in the first half of 2016. Additionally, the Company announced today that a Phase 1 trial with a subcutaneous formulation of XmAb7195 is planned for 2016.
Bispecific Oncology Pipeline
Xencor's initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T-cells for highly potent and targeted killing of malignant cells. XmAb Fc domains confer long circulating half-lives on the antibodies, up to a week in mice, and enable fine-tuning of the potency of the T-cell killing, potentially improving the tolerability of cancer immunotherapy.
Today, Xencor announced that it has selected XmAb13676, a CD20xCD3 bispecific antibody, for clinical testing for B-cell malignancies and expects to begin trials in 2016. This candidate joins XmAb14045, a CD123xCD3 bispecific antibody, and is the second of a growing portfolio of additional XmAb bispecific drug candidates which the Company plans to develop. In addition, the Company will introduce its efforts to modulate T-cell function with new bispecific approaches to target multiple checkpoint inhibitors and to target regulatory T-cells.
Tyler Curiel, M.D., M.P.H., Skinner Chair in Cancer Immunotherapy and Professor of Medicine, University of Texas Health Sciences Center San Antonio will review efforts to reprogram T-cells in oncology therapy and to understand points of intervention for T-cell targeting therapies.